Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer.
BACKGROUND
No useful predictor of resistance or sensitivity to second-line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S-transferase-pi (GST-pi) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemotherapy.


METHODS
Tumor samples were obtained from 26 patients with relapsed epithelial ovarian cancer 3-4 weeks before the initiation of second-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-pi in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay.


RESULTS
The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7%) significantly exceeded that for the nonresponders (9.1%). Expression of GST-pi by immunohistochemical staining was more frequently observed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). Western blot analysis detected GST-pi in all cases. There was no significant difference in the relative density values of the GST-pi Western blot analysis between the two groups. The mean value of GSH concentration in nonresponders was significantly higher than in responders (18.4 +/- 9.7 vs. 7.5 +/- 8.2 microg/mg protein). GSH concentration was below the cutoff point (10.3 microg/mg protein) in all responders except one.


CONCLUSIONS
Second-line chemotherapy consisting of etoposide and cisplatin is effective in the treatment of relapsed epithelial ovarian cancer. In addition, tumor concentration of GSH may be a useful predictor of the response to this therapy.
Kigawa
J
J
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
Minagawa
Y
Y
Kanamori
Y
Y
Itamochi
H
H
Cheng
X
X
Okada
M
M
Oishi
T
T
Terakawa
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002945:Cisplatin / Q000627:therapeutic use; D018282:Cystadenocarcinoma, Mucinous / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D005047:Etoposide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin